Lipoprotein lipase is an enzyme present on the endothelial surface of capillaries which hydrolyzes circulating lipoprotein triglycerides into free fatty acids (FFA) and monoacylglycerol. In adipose tissue, LPL (ATLPL) provides FFA for storage in adipocytes. In skeletal muscle, LPL (SMLPL) provides FFA for oxidation. In hibernating animals, smlpl is relatively higher in the summer than winter (promoting fat oxidation) while the opposite is seen with ATLPL (relatively higher in the winter promoting fat storage. Because in humans an increase in weight often occurs in the winter, this study was designed to determine if there is tissue-specific seasonal variation in LPL in humans. Thirteen normal weight subjects were enrolled in paired studies in which they were assessed in the summer and the winter. All subjects underwent vastus lateralis muscle biopsy and gluteal adipose tissue biopsy for measurement of LPL activity, evalauation of cardiorespiratory fitness by CO2 max and determination of body composition by hydrostatic weighing. Data are expressed as mean =/- sem. ATLPL increased four fold from summer to winter. Overall SMLPL showed no change. Of interest, no change in body weight, body composition, fitness or dietary macronutrient composition over the two days preceding the study was seen. In summary, ATLPL is seasonally regulated. This substantial increase in ATLPL in winter was not related to a change in physical activity, body composition or dietary differences immediately preceding each study. The mechanism behind this variation has yet to be elucidated. However, increases in ATLPL even in the absence of changes in smlpl favors lipid storage over lipid oxidation in the winter.